Association between visit-to-visit variability of HbA_1c and cognitive decline: a pooled analysis of two prospective...

The aim of this study was to investigate the association between visit-to-visit variability in HbA_1c and cognitive function decline in the elderly population.

We performed a pooled analysis of two prospective population-based cohorts (the Health Retirement Study [HRS] and the English Longitudinal Study of Ageing [ELSA]). Cognitive function, including memory and executive function, were assessed at baseline and every 2 years, while HbA_1c levels were assessed at baseline and every 4 years. Visit-to-visit variability (VVV) in HbA_1c was calculated using the CV, SD and variation independent of the mean (VIM) during the follow-up period. Linear mixed models were used to evaluate the association between HbA_1c variability and cognitive function decline with adjustment for demographics, mean HbA_1c, education, smoking, alcohol consumption, BMI, baseline hypertension, baseline diabetes status and HDL-cholesterol.

The study enrolled 6237 participants (58.23% women, mean age 63.38 ± 8.62 years) with at least three measurements of HbA_1c. The median follow-up duration was 10.56 ± 1.86 years. In the overall sample, compared with the lowest quartile of HbA_1c variability, participants in the highest quartile of HbA_1c variability had a significantly worse memory decline rate (-0.094 SD/year, 95% CI -0.185, -0.003) and executive function decline rate (-0.083 SD/year, 95% CI -0.125, -0.041), irrespective of mean HbA_1c values over time. Among individuals without diabetes, each 1-SD increment in HbA_1c CV was associated with a significantly higher rate of memory z score decline (-0.029, 95% CI -0.052, -0.005) and executive function z score decline (-0.049, 95% CI -0.079, -0.018) in the fully adjusted model.

We observed a significant association between long-term HbA_1c variability and cognitive decline among the non-diabetic population in this study. The effect of maintaining steady glucose control on the rate of cognitive decline merits further investigation.